Infectious diseases continue to cause an unacceptably high morbidity and mortality among elderly, critically ill, and hospitalized patients. Animal and human studies imply a significant gender-related influence on both susceptibility to and mortality from infection. All clinical studies to date, however, have been either small or based on retrospective information. One explanation for these possible differences in outcome supported by animal studies is that modulation of circulating levels of estradiol and testosterone may be immunologically "protective," mediated by changes in cytokine and biologically reactive intermediary response. Another possibility is that gender differences in social/ family values are determinants of patient death, including mode of death (withdrawal of support vs. irreversible physiologic collapse) and assumptions regarding the likelihood of long-term, high quality of life survival. The hypothesis to be tested (generated from preliminary data) is that although the incidence of infection is similar for men and women after controlling for admission diagnosis and severity of illness, high estradiol levels in both sexes is associated with higher mortality, and that mortality will also be highly dependent on end of life decisions among other social variables. Aim 1. To prospectively determine the incidence of and associated mortality from hospital-acquired infections in a critically ill population after controlling for multiple pre-defined confounding variables, including gender. Aim 2. To determine the relationship between sex hormonal status, systemic cytokine levels, and the incidence of and outcome from hospital-acquired infections, as well as the relative contribution of infection and end of life decisions to outcome in patients dying under study. Data obtained from this research will be used to design interventional studies utilizing hormonal manipulation, i. e., replacement or blockade, to improve outcomes from otherwise lethal infectious diseases.